An approach to the synthesis of benzo[j]fluoranthene natural products

Natural products bearing benzo[j]fluoranthene skeleton can be found in the metabolites of various fungi and mostly in xylariaceous fungi. They possess a differently oxygenated and/or reduced benzo[j]fluoranthene nucleus. Some representative compounds are bulgarein1, bulgarhodin1, hortein, xylarenol, xylarenoic acid, hypoxylonols A and B, daldinones A-D and truncatone. These compounds show interesting biological activities e.g. topoisomerase I inhibition for Bulgarein2, cytotoxicity for daldinone C and D,3 and tyrosine kinase inhibition for other compounds. Despite their interesting biological activities, to our knowledge, no attempt to synthesize any of these compounds has been described in the literature. Herein we report a synthetic approach carried out for the construction of the benzo[j]fluoranthene skeleton. As the chemistry of acenaphthene is rather well known, the synthetic pathway developed started from commercially available naphthosultone. Suzuki coupling and intermolecular benzoin condensation of two aldehydes are used as key reaction steps to construct the oxygenated benzo[j]fluoranthene skeleton. Due to its modular nature, the developed synthetic route allowed the preparation of a representative derivative and could be adopted for the synthesis of other natural products of this class.